Development and Validation of Point-of-Care Tests for Tuberculosis

项目摘要 结核病是世界上第二大致命传染病，仅次于 艾滋病毒/艾滋病的及时、准确的诊断是有效控制结核病所必需的，但在地方性结核病中， 在某些地区，患者管理最初基于临床怀疑和低敏感性痰液 显微镜炎性培养检测是缓慢的，昂贵的，并且不是常规可用的。有 目前缺乏早期诊断测试，当与边缘临床实验室结合时， 基础设施，可能导致结核病诊断不足或过度。前者影响成功 病人的结果和努力阻止二次传播，而后者促进 不必要的治疗和医疗资源利用率低。新结核病的数量 在美国确诊的病例仍然相当大，其中很大一部分感染发生在 在获得医疗保健机会有限、在外国出生和/或感染艾滋病毒的个人中。 我们组建了一个由临床医生、结核病专家、免疫学家和化学家组成的团队， 结核病的新检测方法使用表面增强拉曼光谱（Sers）来显著降低 检测限，我们建议开发一种廉价，快速，准确的点- 利用多重单克隆抗体同时 鉴定一组已在体内鉴定结核分枝杆菌靶抗原 活动性感染期间的液体。预期配对试验可检测M.结核抗原 将显著提高抗原检测的总体灵敏度， 重新定义结核病的管理方式。这种方法预计将提供定性和 在各种环境中进行快速、可靠诊断所需的定量数据， 及时准确地治疗结核病，并立即采取感染控制措施， 避免传染给他人。该方法的影响被放大，因为Sers平台可以 通过改变检测阵列， 抗体的

PROJECT SUMMARY Tuberculosis (TB) is the world's second deadliest infectious disease, overshadowed only by HIV/AIDS. A prompt, accurate diagnosis is required for effective control of TB, but in endemic regions, patient management is initially based upon clinical suspicion and low-sensitivity sputum microscopy. Confirmatory culture testing is slow, costly, and not routinely available. There is currently a lack of early diagnostic tests, which, when combined with marginal clinical laboratory infrastructure, can result in the under- or over-diagnosis of TB. The former impacts successful patient outcomes and efforts to block secondary transmission, while the latter promotes unnecessary treatment and poor utilization of healthcare resources. The number of new TB cases diagnosed in the U.S. remains sizable, with a significant proportion of infections occurring in individuals who have limited access to health care, are foreign-born, and/or are HIV-infected. We have assembled a team of clinicians, TB experts, immunologists, and chemists to develop a new test for TB. Using surface-enhanced Raman spectroscopy (SERS) to significantly lower the limit of detection, we propose the development of an inexpensive, rapid, and accurate point-of- care immunodiagnostic assay utilizing multiplexed monoclonal antibodies to concurrently identify a panel of Mycobacterium tuberculosis target antigens that have been identified in body fluids during active infection. It is anticipated that a paired test to detect M. tuberculosis antigens in both serum and urine will significantly improve the overall sensitivity of antigen detection, redefining the way TB is managed. This approach is expected to provide the qualitative and quantitative data necessary for rapid, reliable diagnosis in a variety of settings, allowing the prompt accurate treatment of TB, as well as immediate infection control measures designed to avert transmission to others. The impact of the approach is amplified as the SERS platform can be adapted to the diagnosis of other infectious diseases by changing the array of detection antibodies.